Journée des Industriels du Réseau TRIGGERSEP B. François CHU Limoges

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1 Journée des Industriels du Réseau TRIGGERSEP B. François CHU Limoges Mercredi 3 juin 2015 Institut Pasteur Paris

2 Why a sepsis network is needed? Sepsis places a burden on the healthcare system: 300 per 100,000 in-habitants in North America (Angus NEJM 2013) and in Europe (Annane Lancet 2005) Increasing incidence (ageing, immunosuppressive therapy) Kills about 25 to 40% of patients Lack of well-organized academic networking identified as one reason for: More than 3 decades of negative trials Failure to identify any specific treatment for sepsis Clinical research is particular by several aspects: Population, e.g. syndrome and not disease Timing issues, e.g. unscheduled 24/7 inclusions Ethical issues, e.g. waiver for consent

3 CRICS Clinical Research in Intensive Care and Sepsis CICs Sepsis oriented TRIGGERSEP TRIal Group for Global Evaluation and Research in SEPsis

4 CRICS From a regional to a national network BRUXELLES ARGENTEUIL STRASBOURG HAUTEPIERRE LA ROCHE / YON ORLEANS TOURS POITIERS DIJON STRASBOURG NHC 2007 : CRICS 1 (6 ICUs) 2010 : CRICS 2 (10 ICUs) LIMOGES 2012 : CRICS 3 (12 ICUs) ANGOULEME MONTAUBAN Recruiting capacity: >10,300 admissions per year (60% of ventilated patients) CeNGEPS evaluation (2013): A+ 4

5 CICs Sepsis oriented or Sepsis friendly

6 CICs Specificities CIC1435 (Limoges) Linked with ICU Organization expertise in Emergency Trials field Coordination of CRICS effector network CIC1415 (Tours) Statistic expertise Methodological involvement in CRICS academic research Critical Care Medicine identified as an axis CIC1414 (Rennes) Data management and biostatistics in Sepsis therapeutic trials Pharmacology and pharmaco-epidemiology of Sepsis Specific team Pharmacology of Sepsis and septic shock [quadrennial ] CIC1429 (Garches) Scientific expertise of the coordinating physician in therapeutic trials on Sepsis CIC1417 (Cochin Pasteur) Scientific expertise in vaccines with possible development High dynamic of research of the site in Resuscitation and Sepsis field

7 Partners

8 Expertise: Clinical Trials Design and Coordination - Sepsis Expertise: Logistical Research Coordination - Sepsis Expertise: Scientific Coordination Sepsis Jean-Paul Mira WP3 «Scientific Board» Leader Bruno François Co-Coordinator and WP2 «Investigation Support» Leader Djillali Annane Coordinator Pierre-François Dequin WP1 «Clinical Investigation Support» Leader Expertise: Clinical Investigation Coordination Pierre-François Laterre Expertise: Sepsis Trial Europe Interaction WP4 Expertise: Basic Research, Sepsis Jean-Daniel Chiche Genomic Research Sylvie Chevret Responsible for development on new trial design for Sepsis Guillaume Monneret Immunology and Cytometry exploration Fabrice Chrétien Neuro-Immunology and Histology Expertise: Human and animal model Histopathology Experimental pathology - Neuropathology Expertise: Biostatistics, Clinical Trials, Cohort Studies, Prognosis Expertise: Immunology of Sepsis

9 Expertise and capabilities Scientific expertise Investigation network fully adaptable High level biostatistics Basic science expertise Genomic Immuno-monitoring and cytometry Neuro-immunology and histology

10 Scientific Project Toward personalized medicine for sepsis! Individual vs. population-based approach Biomarkers Immuno-Monitoring Genomic Innovative tools for sepsis investigations Databases Datamining / Big data Adaptive designs Research on the influence of qualitative aspects of investigation centres

11 Organization

12 PMO, Mgt board, Communication Full time project manager Monthly TC Participation to all F-CRIN activities Brainstorm meeting to elaborate new projects Dedicated website

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14 Emergency department collaboration (I) Key player for Sepsis: Increasing role of emergency department in hospital patient flow Most of community Sepsis admitted through ED Absence of true Emergency research network Organisationnal and research complexity: Numerous similarity with ICU Patient flow much higher Numerous physician with a 24/7 shift Important unmet medical need: Biomarkers Early treatment approach

15 Emergency department collaboration (II) Previous successful collaboration: TESS study (PHRC 2009): Pharmaco-epidemiological study 3642 patients enrolled Septiflux 2 (PHRC 2013) Biomarker evaluation 1100 patients enrolled Ongoing networking through current ongoing biomarker study Twin approach with ICUs in order to propose a full investigation package

16 Interest for pharmaceutical companies Tailored and customized collaboration Phase II & Phase III (Phase I possible through CICs) Privileged access to Clinical Coordination Center All inclusive approach : Scientifc advise Protocol design Data and biostatistics with easy access to F-CRIN plateform Site selection through existing networks Feasibilities Overcost calculations Boards (DSMB, EAC, CEC.)

17 Collaboration and contracting Direct collaboration with the network within a global Inserm contract or trough individual contract with partners and site Unique point of contact (PMO) Use of unique contracting approach with investigation sites Collaborative trial management with pharma companies through executive steering committee (previous experience)

18 European interaction Previous and numerous European collaborative experience Contact and access to both networks and European scientific societies Expertise in European contracting with sites (IMI example) CLIN-net contact in France ECRIN opportunity as ARO

19 Quality Assurance CICs CRICS Network and partners Inserm-certified Clinical Investigation Centers (CIC) with their own QMS In accordance to local regulations in clinical research and abide by policy of their institutions Inserm-certified research units Own QMS Industrial Partners Own QMS To realize this global QMS: Network governance and responsabilities will be made Quality manager and supervisor will be designated at each structure Inventory of all existing process and documents will be made Network process mapping Network specific documents to be done and applied Continuous improvement by evaluations, audits and process review Regulations ECRIN F-CRIN QMS Industrials Partners CICs TRIGGERSEP QMS Insermcertified research units and laboratories CRICS Network

20 Training Investigators Inter-university Diploma Investigateur en Recherche Biomédicale (Universities of Limoges, Poitiers, Rouen & Tours) Clinical Research staff GCP Investigators Master s degree in Clinical Trials Methodology; 10-hour training module on Intensive Care ; Descartes University, Paris CRA Project of training on ICU specificities for CRO and pharmaceutical companies

21 Network projects European projects 2014 & 2015 TIMES (optimal Management of the very Elderly with Sepsis) (D. Annane) SEPCELL (MSCs in Sepsis CAP related) (P.F. Laterre B. François) Neuro-inflammation and sepsis (F. Chretien) ANR 2014 OCCSUD (D. Annane) PHRC 2014 CAP-CODE (Community-Acquired Pneumonia: COrticosteroids Drug Evaluation (PF. Dequin) CARS (Corticosteroids in ARdS) Brain in Sepsis : Brain functionnal imaging and sepsis (T. Sharshar) PHRC 2015 IMPERIUS: IMmuno-PERsonalIzed therapy during Sepsis (T. Daix)

22 Experience Synergy Merging CRICS and à la carte networks Certification process Continuum from basic science to clinical research Tight interaction with European networks